The Genetics Component will search for susceptibility genes for autism using extended pedigrees identified through the Utah Population Database (UPDB). We have already identified hive pedigrees with 3-7 affected members and large sibships, and have DNA on one pedigree with seven affected cases. UPDB searches for two pedigrees will be performed using 800 new cases of autism ascertained from four sources. DNA from the 800 cases and their parents will be banked for future family-based association studies. Serum and whole blood will also be banked for future serotonin and immune assays. These cases will also provide approximately 40 new sib pairs for network-wide studies and a pol of subjects for network-wide regression studies. Within members of identified extended pedigrees, we will collect phenotypic data on traits that have shown promise in preliminary data as intermediate phenotypes for autism. An intermediate phenotype occurs in unaffected and affected family members, and may serve as a marker for carrier status of susceptibility genes for autism. These traits may help us to identify specific susceptibility genes associated with particular intermediate phenotypes. Preliminary studies suggest several promising intermediate phenotypes, including the Broader Autism Phenotypes (BAP; mild clinical symptoms in communication, social, and behavioral domains), serotonin levels from blood, and head circumference. Immune phenotypes will be identified by the Immune Component; serum for immune assays will be stored on all subjects. A 5 cM genotype scan will be done using the Marshfield Mammalian Genotyping Service. Pedigrees will be analyzed using the clinical phenotype and intermediate phenotypes to map susceptibility loci. Four candidate genes under linkage peaks will be genotyped using SNPs. Budget resources will also be reserved to SNP type the best candidate gene identified through microarray studies in the Immune Component, for a total of five candidate genes.